3-methoxy-4-[3-(4-toluenesulfonyl)propoxy]benzaldehyde | 656810-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-methoxy-4-[3-(4-toluenesulfonyl)propoxy]benzaldehyde
• 英文别名: 4-(3-tosyloxypropoxy)-3-methoxybenzaldehyde；3-(4-Formyl-2-methoxyphenoxy)propyl 4-methylbenzene-1-sulfonate；3-(4-formyl-2-methoxyphenoxy)propyl 4-methylbenzenesulfonate
• CAS: 656810-10-5
• 化学式: C₁₈H₂₀O₆S
• 分子量: 364.419
• InChiKey: LUEPQDKXVJLIIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-methoxy-4-[3-(4-toluenesulfonyl)propoxy]benzaldehyde 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Curcumin and Dehydrozingerone Derivatives:  Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging^†

  摘要：

  Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (A beta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K-i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for A beta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [F-18]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [F-18]8 is metabolically stable in the brain. These results suggest that [F-18]8 is a suitable radioligand for A beta plaque imaging.

  DOI：

  10.1021/jm0607193
• 作为产物：
  描述：

  silver(I) 4-methylbenzenesulfonate 、 4-(3-bromopropoxy)-3-methoxybenzaldehyde 以 乙腈 为溶剂， 以85%的产率得到3-methoxy-4-[3-(4-toluenesulfonyl)propoxy]benzaldehyde
  参考文献：
  名称：

  Curcumin and Dehydrozingerone Derivatives:  Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging^†

  摘要：

  Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (A beta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K-i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for A beta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [F-18]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [F-18]8 is metabolically stable in the brain. These results suggest that [F-18]8 is a suitable radioligand for A beta plaque imaging.

  DOI：

  10.1021/jm0607193

文献信息

• Target Guided Synthesis of 5-Benzyl-2,4-diamonopyrimidines: Their Antimalarial Activities and Binding Affinities to Wild Type and Mutant Dihydrofolate Reductases from <i>Plasmodium falciparum</i>
  作者：Chawanee Sirichaiwat、Chakapong Intaraudom、Sumalee Kamchonwongpaisan、Jarunee Vanichtanankul、Yodhathai Thebtaranonth、Yongyuth Yuthavong

  DOI：10.1021/jm0303352

  日期：2004.1.1

  The resistance to pyrimethamine (PYR) of Plasmodium falciparum arising from mutation at position 108 of dihydrofolate reductase (pfDHFR) from serine to asparagine (S108N) is due to steric interaction between the bulky side chain of N108 and Cl atom of the 5-p-Cl aryl group of PYR, which consequently resulted in the reduction in binding affinity between the enzyme and inhibitor. Molecular modeling suggested that the flexible antifolate, such as trimethoprim (TMP) derivatives, could avoid this steric constraint and should be considered as new, potentially effective compounds. The hydrophobic interaction between the side chain of inhibitor and the active site of the enzyme around position 108 was enhanced by the introduction of a longer and more hydrophobic side chain on TMP's 5-benzyl moiety. The prepared compounds, especially those bearing aromatic substituents, exhibited better binding affinities to both wild type and mutant enzymes than the parent compound. Binding affinities of these compounds correlated well with their antimalarial. activities against both wild type and resistant parasites. Molecular modeling of the binding of such compounds with pfDHFR also supported the experimental data and clearly showed that aromatic substituents play an important role in enhancing binding affinity. In addition, some compounds with 6-alkyl substituents showed relatively less decrease in binding constants with the mutant enzymes and relatively good antimalarial. activities against the parasites bearing the mutant enzymes.
• Curcumin and Dehydrozingerone Derivatives:  Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging^†
  作者：Eun Kyoung Ryu、Yearn Seong Choe、Kyung-Han Lee、Yong Choi、Byung-Tae Kim

  DOI：10.1021/jm0607193

  日期：2006.10.1

  Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (A beta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K-i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for A beta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [F-18]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [F-18]8 is metabolically stable in the brain. These results suggest that [F-18]8 is a suitable radioligand for A beta plaque imaging.